Introduction

Anal cancer accounts for 2% of malignant neoplasms of the gastrointestinal tract. Most cases are squamous cell carcinoma, and the global incidence is increasing alongside the rise in Human Papillomavirus (HPV) incidence. Individuals infected with HPV, particularly those co-infected with human immunodeficiency virus (HIV), as well as smokers, individuals with more than ten sexual partners, and those who maintain receptive anal intercourse are at increased risk of developing this cancer.

Aims & Methods

Our objective was to analyze the trends in anal cancer mortality rates in Brazil from 2012 to 2021, with a focus on gender and age. This descriptive study of anal cancer deaths (ICD-10 code C21) in Brazil utilized data from the Mortality Information System of the Unified Health System (DATASUS)

Results

In Brazil, from 2012 to 2021, there were a total of 5,955 deaths attributed to anal cancer, with 3,600 deaths in women and 2,355 deaths in men, and most of these deaths occurred after the age of 50. During this period, anal cancer mortality rates increased in both sexes. In 2012, the mortality rate was 0.22 deaths per 100,000 women and 0.13 deaths per 100,000 men, rising to 0.55 deaths per 100,000 women and 0.48 deaths per 100,000 men by 2021. Furthermore, the average annual percent change (AAPC) in anal cancer mortality rates was higher in males than females across all age groups except for ages 30-39. In males aged 40 and over, the AAPC of anal cancer mortality rates increased progressively with age, while in females, it remained stable across different age groups. Notably, among individuals over 80 years old, the AAPC was 11% per year among women and 44% per year among men. As a result, the mortality ratio between women and men decreased from 1.88 (2012-2016) to 1.41 (2017-2021), reaching its lowest value of 1.14 in 2021.

Conclusion

Despite its rarity, anal cancer warrants recognition due to its rising mortality rates. While initially, mortality rates from anal cancer were significantly higher among women, the accelerated increase in mortality rates among men has led to similar mortality rates between genders by the year 2021.

References

1. Roberts JR, Siekas LL, Kaz AM. Anal intraepithelial neoplasia: A review of diagnosis and management. World J Gastrointest Oncol. 2017;9(2):50-61.
2. Itarat Y, Kietpeerakool C, Jampathong N, Chumworathayi B, Kleebkaow P, Aue-Aungkul A, Nhokaew W. Sexual behavior and infection with cervical human papillomavirus types 16 and 18. Int J Womens Health. 2019;11:489-494.
3. De Vuyst H, Clifford GM, Nascimento MC, et al: Prevalence and type distribution of human papillomavirus in carcinoma and intraepithelial neoplasia of the vulva, vagina and anus: A meta-analysis. Int J Cancer 124:1626-1636, 2009.
4. Oliveira CR, Niu YS, Einarsdottir HM, Niccolai LM, Shapiro ED. Disparities in the Epidemiology of Anal Cancer: A Cross-Sectional Time Series. Health Equity. 2020 Sep 16;4(1):382-385.
5. Pérez-González A, Cachay E, Ocampo A, Poveda E. Update on the Epidemiological Features and Clinical Implications of Human Papillomavirus Infection (HPV) and Human Immunodeficiency Virus (HIV) Coinfection. Microorganisms. 2022;10(5):1047.
6. Kost BP, Hofmann J, Stoellnberger S, Bergauer F, Blankenstein T, Alba-Alejandre I, Stein A, Stuckart C, Weizsäcker K, Mylonas I, Mahner S, Gingelmaier A. Prevalence of human papillomavirus infection of the anal canal in women: A prospective analysis of high-risk populations. Oncol Lett. 2017;13(4):2495-2501.

Disclosure

there's no conflict of interest

Introduction

Colorectal cancer (CRC) is the second most common cancer and the third leading cause of cancer-related deaths in Brazil. High-income countries with organized screening programs have achieved significant reductions in CRC mortality in the last decades through early detection, polypectomy, and improved therapeutic interventions. Meanwhile, several low- and middle-income nations continue to experience rising incidence and persistently high mortality rates. Understanding CRC mortality patterns across different age groups and sexes is essential to guide public health policies and optimize resource allocation for prevention, early detection, and treatment strategies.

Aims & Methods

This study aimed to analyze CRC mortality trends in Brazil from 2012 to 2021. We conducted a descriptive analysis of CRC-related deaths (ICD-10 codes C18, C19, and C20) using data from the Mortality Information System of the Unified Health System (DATASUS). The crude annual mortality rate (deaths per 100,000 inhabitants) was calculated by dividing the number of deaths by the estimated population provided by the Brazilian Institute of Geography and Statistics (IBGE). We also analyzed annual mortality rates by age range and sex and calculated the average annual percent change (AAPC) in mortality rates to assess trends over time.

Results

A total of 175,159 CRC-related deaths were recorded in Brazil between 2012 and 2021, with 86,330 occurring in men and 88,829 in women. Among men, 27.4% of deaths occurred before age 60, 53.8% between ages 60 and 79, and 18.8% at age 80 or older, while among women, these proportions were 27.4%, 47.1%, and 25.5%, respectively. During this period, CRC mortality rates increased in both sexes, rising from 7.06 to 9.73 deaths per 100,000 men and from 7.29 to 9.16 deaths per 100,000 women. Consequently, the male-to-female mortality ratio grew from 0.97 in 2012 to 1.06 in 2021, leading to a slight predominance of male gender at the end of the assessed period. The AAPC in mortality was higher in men than in women across all age groups, except for those aged 40–59 years (Table 1). Among younger individuals, those aged 30–39 years had a low absolute mortality rate (<0.4 deaths per 100,000 inhabitants) but showed the highest AAPC (3.5% per year in men and 2.8% per year in women). Among individuals within the recommended CRC screening age range, the highest AAPC was observed in those aged 60–69 years (2.1% per year in men and 1.7% per year in women).

Conclusion

The concerning rise in CRC mortality in Brazil underscores the need for enhanced public health strategies, including improved access to screening and better healthcare resources. Additionally, the greater increase in mortality rates from early-onset colorectal cancer, particularly between ages 20 and 39, warrants attention, with a focus on identifying high-risk individuals and addressing modifiable risk factors in the population.

Table 1 –Average annual percent change in colorectal cancer mortality rate by sex and age range.

Introduction

Emerging evidence points towards a plausible link between psoriasis, a common chronic inflammatory skin disease, and inflammatory bowel disease (IBD), as both diseases share similar inflammatory pathways(1).

Aims & Methods

Our aim was to identify patterns and potential predictors for the development of IBD in a psoriasis patients cohort.
This retrospective electronic health records-based study utilized data from the Meuhedet Health Maintenance Organization (MHMO) which contains 20 years of continuous follow-up. Patents’ data were evaluated for demographic parameters, comorbidities, auto-antibodies, and medications used.
Prevalence and incidence of IBD were measured. The association between psoriasis and IBD was evaluated using both univariate and multivariate logistic regression models, with adjustments made for possible confounding factors. The prediction model was developed to identify predictors of IBD development in psoriasis

Results

Data between psoriasis patients (n=61,003) and age and gender-matched controls (n=244,012) was compared.
Among psoriasis patients, 2.5% were diagnosed with IBD, compared to 1.6% of controls (OR 1.57, 95%CI 1.48-1.67). The adjusted OR was 1.47 (95% CI 1.37-1.56), p<0.001. IBD was diagnosed before the onset of psoriasis in 51.9% and within 1 year of psoriasis onset in 7.2%. Predictors of IBD development in psoriasis patients were: older age (OR 1.01, 95%CI 1.01-1.02), male gender (OR 1.22, 95%CI 1.03-1.45), axial spondyloarthropathies (OR 1.78, 95%CI 1.29-2.45), severe psoriasis (OR 16.03, 95%CI 11.02-23.34), uveitis (OR 3.13, 95%CI 2.08-4.71), ASCA positivity (OR 10.71, 95%CI 7.38-15.55), and P-ANCA positivity (OR 7.71, 95%CI 2.04-29.04). The specific risk for IBD among psoriasis patients according to disease severity is shown in Table 1.
Decreased risk for IBD in psoriasis patients was observed in patients with obesity (OR 0.76, 95%CI 0.62-0.94), psoriatic arthritis (OR 0.49, 95%CI 0.34-0.72), phototherapy (OR 0.09, 95%CI 0.06-0.15), and methotrexate use (OR 0.13, 95%CI 0.08-0.21). The presence of ANA antibodies was not significantly associated with the risk of IBD within the psoriasis cohort.

Conclusion

Our study provides evidence for a significant association between psoriasis and IBD and identifies several predictors for the development of IBD in psoriasis patients. These findings may improve clinical decision-making and patients’ outcomes.

References

Li, Y., Guo, J., Cao, Z., & Wu, J. (2022). Causal Association Between Inflammatory Bowel Disease and Psoriasis: A Two-Sample Bidirectional Mendelian Randomization Study. Frontiers in immunology, 13, 916645. https://doi.org/10.3389/fimmu.2022.916645

Disclosure

None

Introduction

Ulcerative colitis (UC) treatment requires a patient-centric efficacy endpoint to assess treatment benefits, enabling a shift towards a personalized approach. Comprehensive disease control (CDC) is an individual multi-component endpoint based on findings from a patient and expert Delphi consensus on remission assessment in UC. CDC was defined as IBDQ remission, partial Mayo Clinic Score (pMCS) remission, biomarker (faecal calprotectin [FCP]) remission and endoscopic improvement.

Aims & Methods

We evaluated different definitions of CDC, and the contribution of different CDC components to the net treatment benefit (NTB) of filgotinib 200 mg (FIL200), an oral, once-daily, Janus kinase 1 inhibitor approved for UC treatment following the SELECTION trial (NCT02914522). CDC was assessed at week 58 (W58) of SELECTION in adult patients with active UC treated with FIL200 or placebo (PBO). The CDC definitions evaluated were: 4-component CDC (CDC4) with FCP <150 µg/g, CDC4-150; CDC4 with FCP <250 µg/g, CDC4-250; 5-component CDC (with histological remission [CDC5]) with FCP <150 µg/g, CDC5-150; and CDC5 with FCP<250 µg/g, CDC5-250. The proportion of patients achieving each combination of components was evaluated. NTB of FIL200 was assessed for each endpoint using generalized pairwise comparisons and is reported here for CDC4-150 (and excluding different components).

Results

At W58, 21.6%, 26.6%, 19.1% and 22.6% of FIL200-treated patients achieved CDC4-150, CDC4-250, CDC5-150 and CDC5-250, respectively. Among patients who did not achieve CDC4-150, 0.5% of patients did not achieve this composite endpoint because they did not achieve pMCS remission; whereas 5.0%, 10.1% and 6.0% did not do so because they did not achieve IBDQ remission, biomarker remission or endoscopic improvement, respectively. Positive overall NTB of FIL200 versus PBO was demonstrated with all CDC definitions, including those with histological remission (CDC5). For CDC4-150 at W58, excluding pMCS remission did not substantially change the NTB (Δ −0.33; Table) versus excluding IBDQ or biomarker remission, or endoscopic improvement (Δ 3.87, 6.93 and 3.20, respectively). Similar NTB results were seen for all CDC definitions, with or without histological remission.

Conclusion

CDC is a stringent, patient-level, multi-component endpoint achieved by ~1/5 of FIL200-treated patients at W58. While CDC4-150 could be the optimal operational definition, the addition of histological remission resulted in similar stringency, potentially allowing for the use of different CDC definitions based on context or resources. Additional NTB of FIL200 was identified in patients when IBDQ or biomarker remission or endoscopic improvement were excluded. Overall, CDC appears to be a suitable endpoint to assess individual comprehensive benefit in patients with UC. Prospective validation is needed.

Table. NTB with exclusion of different components of the CDC4-150 endpoint.

Disclosure

We thank Katrien Van Beneden for her contribution to conceptualization, investigation and data interpretation.
The SELECTION trial was sponsored by Gilead Sciences, Inc. (Foster City, CA, USA). Galapagos NV (Mechelen, Belgium) was a collaborator for the SELECTION trial and funded this analysis.
Medical writing support for the development of this abstract was provided by Hannah Stephens, PhD, of PharmaGenesis London, London, UK, and was funded by Alfasigma S.p.A.
VV and AO are employees of Alfasigma S.p.A at the time of abstract submission
SS has received personal fees from AbbVie, Amgen, Arena Pharmaceuticals, Biogen, Bristol Myers Squibb, Celgene, Celltrion, Dr Falk Pharma, Eli Lilly, Ferring Pharmaceuticals, Fresenius Kabi, Galapagos/Gilead Sciences, I-Mab, Janssen Pharmaceuticals, MSD, Mylan, Pfizer, Protagonist, Provention Bio, Sandoz/Hexal, Takeda, Theravance Biopharma and UCB.
BGF has received grants and personal fees from AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Janssen Biotech/Centocor, Johnson & Johnson/Janssen, Pfizer, Receptos and Takeda; and personal fees from Ablynx, ActoGeniX, Akebia Therapeutics, Inc., Allergan, Atlantic Pharmaceuticals, Avaxia Biologics, Inc., Avir Pharma, Baxter Healthcare Corporation, Biogen Idec, BiomX Israel, Boehringer Ingelheim, Boston Pharmaceuticals, Calypso Biotech, Celgene, Elan/Biogen, Eli Lilly, enGene, Ferring Pharmaceuticals, Galapagos, Genentech/Roche, gIcare Pharma, Gilead Sciences, Given Imaging, Gossamer Bio, GSK, Inception IBD, Inc., Ironwood Pharmaceuticals, Japan Tobacco Company, Kyowa Hakko Kirin Co. Ltd, Lexicon Pharmaceuticals, Lycera, Mesoblast, Millennium Pharmaceuticals, MSD, Nestlé, Nextbiotix, Novartis, Novo Nordisk, Par’Immune, Progenity, Prometheus, Protagonist, Qu Biologics, Q32 Bio (formerly AdMIRx, Inc.), Salix Pharmaceuticals, Shire, Sienna Biopharmaceuticals, Sigmoid Pharma, Synergy Pharma, Teva Pharmaceuticals, TiGenix, Tillotts Pharma, UCB, Vertex Pharmaceuticals, VHsquared, Vivelix Pharmaceuticals, Wyeth, Zealand Pharma and Zyngenia.
SV receives financial support for research from AbbVie, Galapagos, Johnson & Johnson, Pfizer and Takeda; speaker and/or consultancy fees from AbbVie, Abivax, AbolerIS Pharma, AgomAb Therapeutics, Alimentiv, Arena Pharmaceuticals, AstraZeneca, Bior Therapeutics (formerly Progenity), Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Cytoki Pharma, Dr Falk Pharma, Eli Lilly, Ferring Pharmaceuticals, Galapagos, Genentech-Roche, Gilead Sciences, GSK, Hospira, IMIDomics, Janssen Pharmaceuticals, Johnson & Johnson, Materia Prima, Mestag Therapeutics, MiroBio, Morphic, MRM Health, MSD, Mundipharma, Pfizer, ProDigest, Prometheus, Robarts Clinical Trials, Surrozen, Takeda, Theravance Biopharma, Tillotts Pharma AG, VectivBio, Ventyx Biosciences and Zealand Pharma.
SD reports personal fees from AbbVie, Allergan, Amgen, AstraZeneca, Athos Therapeutics, Biogen, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly, Enthera, Ferring Pharmaceuticals, Gilead Sciences, Hospira, Inotrem, Janssen Pharmaceuticals, Johnson & Johnson, MSD, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity Therapeutics, Takeda, TiGenix, UCB and Vifor Pharma.
MF is an employee and shareholder of Galapagos NV.
VV and AO are former employees and shareholders of Galapagos NV, and employees of Alfasigma. S.p.A.
LP-B has received consulting fees from Abivax, AbbVie, Alimentiv, Alma Bio Therapeutics, Amgen, Applied Molecular Transport, Arena Pharmaceuticals, Biogen, Bristol Myers Squibb, Celltrion, CONNECT Biopharma, Cytoki Pharma, Eli Lilly, Enthera, Ferring Pharmaceuticals, Fresenius Kabi, Galapagos, Genentech, Gilead Sciences, Gossamer Bio, GSK, HAC Pharma, IAG Image Analysis, Index Pharmaceuticals, Inotrem, Janssen Pharmaceuticals, Medac, Mopac, Morphic, MSD, Norgine, Novartis, OM Pharma, ONO Pharma, OSE Immunotherapeutics, Pandion Therapeutics, Par’Immune, Pfizer, Prometheus, Protagonist, Roche, Roivant, Samsung, Sandoz, Sanofi, Takeda, Theravance Biopharma, Thermo Fisher Scientific, TiGenix, Tillotts Pharma, VectivBio, Ventyx, Viatris, Vifor Pharma and Ysopia; grants from Celltrion, Fresenius Kabi and Takeda; and speaking fees from AbbVie, Amgen, Arena Pharmaceuticals, Biogen, Celltrion, Eli Lilly, Ferring Pharmaceutics, Galapagos, Genentech, Gilead Sciences, Janssen Pharmaceuticals, Medac, MSD, Pfizer, Sandoz, Takeda, Tillotts Pharma, Viatris and Vifor Pharma.

Clinical Case Summary

A 62 y/o male complaining from epigastric pain, constipation, vomiting and eructation for two months and CT abd revealed irresectable pancreatic head mass 4.5x4.5 cm encasing PV and SMV with duodenal invasion. Ryle decompression was done before EGD, duodenal obstruction was noted and biopsy showed duodenitis (stasis induced). EUS-FNB confirmed well differentiated AC. Duodenal stenting was successfully performed with improving symptoms.
After one week patient complained from weakness and abnormal gait, examination showed normal vital signs, bilateral lower limb edema and patient was lethargic. Three days after, the patient became confused (GCS 12), so he was admitted to ICU.
CT brain was unremarkable. Lab investigations showed the following:
Na 130, K 4.1, Ca 7.8, Phos 2.8, Mg 2.6, Alb 2.9
Refeeding injury was suspected and TPN was started by the ICU team. No improvement of the consciousness was achieved and patient caught chest infection, developed sepsis and died.
Discussion: Refeeding syndrome is a serious complication that can be easily missed [1] in upper GI malignant obstructions with prolonged decreased oral intake along with the malignancy cachexia status. These obstructions may need surgery or stenting to regain patency and without cautious monitoring of the nutrients repletion rate either enteral or parenteral this will lead to fluid and electrolyte disturbance (Fluid balance abnormalities, Abnormal glucose metabolism, Vitamin deficiency, e.g., vitamin B1 (thiamine), Hypophosphatemia, Hypomagnesaemia and/or Hypokalemia) [2] with symptoms ranging from vague up to life threatening conditions like disturbed conscious level and heart failure. Our patient had high risk of developing refeeding syndrome due to caloric deprivation secondary to duodenal obstruction with development of the symptoms after stenting and restarting oral intake.
Conclusion: Nutritionist counseling after GI stenting of upper GI malignant obstructions is needed to avoid refeeding syndrome.

References

[1] Reber, E., Friedli, N., Vasiloglou, M.F., Schuetz, P. and Stanga, Z., 2019. Management of refeeding syndrome in medical inpatients. Journal of clinical medicine, 8(12), p.2202.
[2] Crook, M.A., Hally, V. and Panteli, J.V., 2001. The importance of the refeeding syndrome. Nutrition, 17(7-8), pp.632-637.

Introduction

Advances in medical management of Crohn’s disease (CD) have improved disease outcomes; however, significant gaps remain. Approximately 30% of patients experience primary non-response to induction therapy with biologics, and over 40% will experience loss of response. There is an urgent need to identify new adjunct therapies, including diet, that can alter the disease course. Dietary patterns characterized by increased intakes of fibre, fruit, vegetables and decreased intakes of processed foods, sugar and omega-6 fatty acids are linked to a reduced prevalence of CD and decreased biomarkers of intestinal and systemic inflammation; however, the effects upon mucosal inflammation are unknown in patients who have lost response to usual medical treatments. We developed the CD Therapeutic Dietary Intervention (CD-TDI), a novel dietary approach incorporating best practices and current evidence to determine its therapeutic potential in reducing inflammation in patients with active CD who have lost response to their usual therapies.

Aims & Methods

This 13-week RCT aimed to explore the efficacy of the CD-TDI compared with conventional management (CM) to reduce clinical disease activity (Harvey-Bradshaw Index (HBI) <5) and reduce mucosal inflammation, as measured by fecal calprotectin (FCP) in mild-to-moderately active luminal CD. Patients with mild to moderately active disease, determined by endoscopic, cross-sectional imaging or FCP >100 ug/g, on stable medical therapy 8 weeks prior to recruitment were eligible to participate (n=28). Upon randomization, the CD-TDI group (n=16) met virtually with a registered dietitian trained in the CD-TDI protocol weekly for 13 weeks. Participants assigned to CM (n=12) followed their habitual diet and met with the same registered dietitian as participants in the CD-TDI group at week 0 (W0) and week 13 (W13) to capture their dietary recall. FCP, HBI, and C-reactive protein (CRP) were assessed at W0 and W13.

Results

Twenty-eight participants (53% females, age 40 years (IQR:31-55); BMI 27 kg/m² (IQR:24-31)) were enrolled. Medical therapy did not differ between groups, with 54% (15/28) of participants receiving no drug therapy, 29% (8/28) 5-ASA monotherapy, 21% (6/28) biologic therapy, 11% (3/28) corticosteroids or 14% (4/28) immunomodulators. At W0, the FCP, HBI and CRP did not differ significantly between groups. In the CD-TDI group, FCP decreased significantly from 130 ug/g (IQR: 38-411) at W0 to 72 ug/g (IQR:3-153) at W13 (p= 0.01) and significantly differed between the CM group at W13 (p=0.04). In a sub-group analysis (n=11) of participants with FCP >250 ug/g at W0, at W13 the FCP decreased significantly from 632 ug/g (IQR: 356-1013) to 166 ug/g, (IQR:52-701) (p=0.06) within the CD-TDI group, however, this same trend was not observed in the CM (W0:337 ug/g IQR:324-1013 vs. W13:431 ug/g, IQR:46-1770, p=0.69). At W13, between-group differences in the CRP were found between the CD-TDI group (1.0 mg/L, IQR:0.6-2.4) and the CM group (4.5 mg/L, IQR:2.6-13.0) (p=0.002). The CD-TDI group experienced a significant decrease in HBI from W0 to W13 (W0: 3.0, IQR:1.0-5.3; W13: 2.0, IQR:0-3.0; p=0.05), however, this was not observed in the CM group.

Conclusion

At W13, the CD-TDI significantly decreased clinical and biochemical markers of inflammation in patients with mild-to-moderately active CD. This preliminary analysis suggests that CD-TDI could be a potential adjunct management strategy for reducing inflammation in CD. We hope to confirm these promising results with an adequately powered sample.